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Mechanisms of Ras signaling in single synapses

Award Number: R01MH080047
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/05/2007
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Mechanisms of Ras signaling in single synapses - ABSTRACT The Ras superfamily of small GTPase proteins is important for many neuronal processes essential to synaptic plasticity, including long-term synaptic potentiation, formation of new synapses, and regulation of cell excitability. Among the Ras superfamily, a particularly important subfamily is a group of proteins called Rab, which regulate trafficking of membrane and glutamate receptors during synaptic plasticity. Consistent with the importance of Rab signaling in synaptic plasticity, abnormal Rab signaling is associated with diseases causing cognitive impairments and learning deficits. However, the spatiotemporal dynamics of Rab proteins during synaptic plasticity and their exact functions at individual dendritic spines are not fully understood. Thus, the objective of this project is to elucidate the mechanisms and roles of Rab protiens in dendritic spines during synaptic plasticity. We have developed highly sensitive biosensors for imaging activity of Rab4, Rab5, Rab8 and Rab10. Our preliminary data suggest that Rab proteins are activated or inactivated in different temporal windows during synaptic plasticity. Based on these preliminary data and previous literatures, our central hypothesis is that Rab proteins regulate the balance of membrane trafficking between different internal membrane compartments in dendritic spines to regulate functional and structural plasticity of dendritic spines, and this in turn modulates synaptic plasticity, learning and memory. In this project, we will further analyze signaling mediated by Rab proteins and their roles in trafficking of membrane and receptors during synaptic plasticity. Our specific aims are 1) to reveal the spatiotemporal dynamics of Rab activity during synaptic plasticity and to identify upstream regulators of Rab proteins, 2) to elucidate the roles of Rab proteins in structure and function of spines and in membrane trafficking during synaptic plasticity, 3) to identify the roles of Rab proteins in glutamate receptor internalization and recycling using biochemical assays, and 4) to elucidate the roles of Rab proteins in synaptic plasticity, learning and memory. This work will advance our understanding of how Rab couples calcium with synaptic plasticity, learning and memory.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$1 )
2024	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	15	5/14/2024	NON-COMPETING CONTINUATION	-$1
2024	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	15	2/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = -$1

Issue Date FY: 2023 ( Subtotal = $566,899 )
2023	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	15	2/1/2023	NON-COMPETING CONTINUATION	$56,690
2023	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	15	12/9/2022	NON-COMPETING CONTINUATION	$510,209
														Subtotal = $566,899

Issue Date FY: 2022 ( Subtotal = $566,899 )
2022	2022	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	14	12/13/2021	NON-COMPETING CONTINUATION	$510,209
2022	2022	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	14	5/10/2022	NON-COMPETING CONTINUATION	$56,690
														Subtotal = $566,899

Issue Date FY: 2021 ( Subtotal = $566,899 )
2021	2021	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	13	4/7/2021	NON-COMPETING CONTINUATION	$56,690
2021	2021	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	13	12/7/2020	NON-COMPETING CONTINUATION	$510,209
														Subtotal = $566,899

Issue Date FY: 2020 ( Subtotal = $596,737 )
2020	2020	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	12	12/24/2019	NON-COMPETING CONTINUATION	$537,065
2020	2020	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	12	3/11/2020	NON-COMPETING CONTINUATION	$59,672
														Subtotal = $596,737

Issue Date FY: 2019 ( Subtotal = $608,317 )
2019	2019	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	11	9/24/2019	COMPETING CONTINUATION	$0
2019	2019	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	11	2/25/2019	COMPETING CONTINUATION	$608,317
														Subtotal = $608,317

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	10	7/11/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $475,000 )
2017	2017	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	10	7/29/2017	NON-COMPETING CONTINUATION	$47,500
2017	2017	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	10	3/10/2017	NON-COMPETING CONTINUATION	$427,500
														Subtotal = $475,000

Issue Date FY: 2016 ( Subtotal = $475,000 )
2016	2016	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	9	3/25/2016	EXTENSION WITH OR WITHOUT FUNDS	$475,000
														Subtotal = $475,000

Issue Date FY: 2015 ( Subtotal = $475,000 )
2015	2015	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	8	2/25/2015	NON-COMPETING CONTINUATION	$475,000
														Subtotal = $475,000

Issue Date FY: 2014 ( Subtotal = $475,000 )
2014	2014	MAX PLANCK FLORIDA CORPORATION	ONE MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	7	3/14/2014	NON-COMPETING CONTINUATION	$475,000
														Subtotal = $475,000

Issue Date FY: 2013 ( Subtotal = $475,000 )
2013	2013	MAX PLANCK FLORIDA CORPORATION	5353 PARKSIDE DRIVE	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	6	5/14/2013	COMPETING CONTINUATION	$475,000
														Subtotal = $475,000

Issue Date FY: 2011 ( Subtotal = $308,880 )
2011	2011	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	001	5	7/11/2011	NON-COMPETING CONTINUATION	$28,080
2011	2011	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	000	5	3/29/2011	NON-COMPETING CONTINUATION	$280,800
														Subtotal = $308,880

Issue Date FY: 2010 ( Subtotal = $312,000 )
2010	2010	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	000	4	3/18/2010	NON-COMPETING CONTINUATION	$312,000
														Subtotal = $312,000

Issue Date FY: 2009 ( Subtotal = $312,000 )
2009	2009	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	000	3	4/9/2009	NON-COMPETING CONTINUATION	$312,000
														Subtotal = $312,000

Issue Date FY: 2008 ( Subtotal = $312,000 )
2008	2008	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	000	2	3/24/2008	NON-COMPETING CONTINUATION	$312,000
														Subtotal = $312,000

Issue Date FY: 2007 ( Subtotal = $311,750 )
2007	2007	DUKE UNIVERSITY	BOX 104135	DURHAM	NC	27708	DURHAM	USA	Mental Health Research Grants	000	1	4/5/2007	NEW	$311,750
														Subtotal = $311,750

Grand Total All Awards = $6,837,380

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Mechanisms of Ras signaling in single synapses

Award Number: R01MH080047

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/05/2007

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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